g-csf pmrd: granulocyte colony stimulating factor (g-csf) stimulated bone marrow and in vivo t-cell depletion in patients with hematologic malignancies or bone marrow failure syndrome

Conditions: Hematologic Malignancies

Summary: the purposes of this study are: * to examine the engraftment rate in patients receiving in vivo t-cell-depleted g-csf stimulated bone marrow from partially mismatched related donors. * to evaluate the incidence and severity of acute and chronic graft-versus-host disease in patients receiving in vivo t-cell-depleted g-csf stimulated bone marrow from partially mismatched related donors.

this study is a single-arm, non-randomized feasibility study. patients meeting the criteria for this study will be entered sequentially until completion or closure of the study. early stopping rules will be employed to ascertain whether an unacceptable rate of toxicity (non-engraftment, and/or acute gvhd) occurs. patients will be prepared for transplant through the administration of the following conditioning regimen based on their primary disease: * total body irradiation (1400 rads in 8 fractionated doses) and high dose chemotherapy, including cytosine arabinoside, etoposide, and cyclophosphamide. patients with bone marrow failure syndrome will not receive etoposide in the conditioning regimen. * post transplant immunosuppression prophylaxis against acute gvhd will include sequential administration of cyclosporine, methotrexate, basiliximab and mycophenolate. * the donor will receive 3 daily g-csf injections prior to marrow harvest starting on day -3. the injections may be initiated by the donor's primary physician prior to donor's arrival, or by the bmt service at children's healthcare of atlanta. * patients will receive daily gm-csf injections (250 mcg/m2) starting from day +7 post transplant until absolute neutrophil count (anc) is greater than 2,000/µl for three days.

Eligibility criteria:
inclusion criteria: * patients with hematologic malignancies or bone marrow failure syndrome who are candidates for allogeneic bone marrow transplantation are eligible for this study. hematologic malignancies indicated for transplantation: * acute lymphoblastic leukemia (all) in first remission (with high risk feature), 2nd or greater remission. * acute myeloid leukemia (aml) in first remission (with high risk feature), 2nd or greater remission. * chronic myeloid leukemia (cml) in 2nd chronic phase or accelerated phase. * juvenile myelomonocytic leukemia (jmml). * myelodysplastic syndrome. * biphenotypic leukemia in first (with high risk feature), 2nd or greater remission. * induction failure leukemia. * refractory relapsed leukemia. * bone marrow failure syndrome. * severe aplastic anemia failed immunotherapy. * patients who do not have a 6 out of 6 matched related or unrelated donor or 4/6 and 5/6 matched cord blood will be eligible for this study. * partially mismatched related donor availability as defined by molecular typing with 3 to 5 hla matches. * patients who are under 22 years of age. exclusion criteria: * patients will not be excluded based on sex, racial, or ethnic background. * patients will be excluded if they demonstrate significant functional deficits in major organs, which would obviously interfere with successful outcome following bone marrow transplant utilizing the following guidelines. * evidence of active, deep-seated, life-threatening infections for which there is no known effective therapy (certain fungal species, hiv, etc.). * patients who have been treated for infections must have appropriate responses as documented by 2 (two) consecutive negative cultures and/or stable radiographic examinations. * patients who have active central nervous system (cns) leukemic disease. * patients will be excluded if they are women of childbearing potential who are currently pregnant (beta-hcg+) or who are not practicing adequate contraception. * patients who have had a previous hematopoietic stem cell transplant will be excluded. * donors will be excluded if they are sensitive to e. coli-derived protein.